Project Abstract: Human cytomegalovirus (HCMV) and Human Herpesvirus 6a (HHV6a) members of the ?-herpesvirus family, are pathogens that have evolved to infect a significant majority of the human population. Both viruses retain the capacity to reactivate from latency, which is highly problematic in immunosupressed populations. These two viruses encode numerous factors that undermine host responses to viral infection and alter the subcellular environment thereby promoting efficient viral replication. This proposal seeks to define the biological role for the microRNAs (miRNAs) encoded by these two viruses. We will evaluate the requirement of each miRNA as well as utilize novel and innovative techniques for RNA and protein labeling within viral infected cells. Successful completion of these aims will fill a significant knowledge gap in our understanding of the viral factors that promote pathogenesis.